The incidence of fungal infections in the immunocompromised population has significantly increased over the past several years. In particular, Candida species, especially Candida albicans, are often significant pathogens in patients infected with human immunodeficinecy virus (HIV). As an example, infections can range from somewhat mild oropharyngeal or vulvovaginal candidiasis to severe debilitating mucocutaneous candidiasis. Moreover, AIDS patients suffering from oral candidiasis may also experience esophageal candidiasis which has been known to lead to gastrointestinal bleeding and perforation. Candida albicans is a species which is commonly isolated from patients with the above-mentioned infections.
Treatment of candidiasis has typically involved two classes of drugs: (1) polyenes such as amphotericin B and nystatin; and (2) azoles such as clotrimazole, ketoconozole, fluconozole, and itraconazole. Since immunosuppression in AIDS-infected patients often occurs over an extended period of time, fungal reinfection may be common. Accordingly, these patients commonly receive prolonged antifungal therapy. Widespread antifungal therapy, however, has raised issues regarding the increased level of resistance among isolates of the Candida species, especially with respect to fluconozole. See Pfaller, M. A., et al., Journal of Clinical Microbiology, January 1994, pp. 59-64; and Cameron, M. L., et al., Antimicrobial Agents and Chemotherapy, November 1993, pp. 2449-2453.
In view of the above, there remains a need in the art to develop new antifungal treatment methods utilizing compounds which address the problems noted above. It would especially be desirable if the use of such compounds displayed increased fungal activity at acceptable dosage levels. Accordingly, it is an object of the present invention to provide new antifungal treatment methods exhibiting increased fungal activity at acceptable dosage levels.